Lens crystallins are structural proteins which comprise over 90% of the total protein in the lens. As a result of the unique metabolism and mode of growth of the lens, the crystallins are very long-lived proteins and tend to accumulate a wide variety of age-related structural modifications. We are interested in the mechanisms by which these modifications arise and the possible role such processes may play in cataract development. Because oxidative stress appears to be responsible for many of the protein changes in the lens, we are investigating a number of oxidative mechanisms which may be active in the eye and which could contribute to the development of senile cataracts or of cataracts associated with other pathological processes within the eye. Specifically, we are investigating the following areas: (1) the possibility that singlet molecular oxygen may be produced within the human lens by the action of near ultraviolet light and endogenous photosensitizers, (2) the possible activation of the hydrogen peroxide present in the aqueous and lens by metal-containing compounds, and (3) the effect of lipid peroxidation products from degenerating retinal tissue on the lens. In other studies of crystallin modification, Dr. Donita Garland is determininig the extent of phosphorylation of crystallins by endogenous kinases. This work is focusing on the possible role of phosphorylation in metabolic regulation and cataract development.